Helicobacter pylori (H. pylori) infection of the stomach is responsible for significant amount of morbidity and mortality. Although H. pylori have multiple virulence factors, the host response also contributes to pathogenesis and these host factors vary between individuals. In addition to H. py/on-associated diseases, significant morbidity is associated with non-H. pylori associated gastric afflictions. Dyspepsia is the most common gastric ailment among adults and children yet there is no clear association with H. pylori. New genomics evidence on bacterial isolates indicates there are other populations of bacteria in the gastric mucosa. These other bacterial genera or species might help explain why gastric maladies vary between populations and between individuals. They might also serve as an important co-factor in H. py/on-associated diseases. We hypothesize that the gastric mucosa harbors resident populations of non-Helicobacter bacteria that vary among individuals and serve as important cofactors in determining the gastric health of the host. These bacteria, together with the host immune response work cumulatively to influence the incidence and character of gastric malignancies. This hypothesis will be tested by accomplishing the following three specific aims. 1) Compare the immune responses to H. pylori in children and adults undergoing diagnostics for presumptive H. pylori infection. These studies will help us assess the relative importance of the key effector immune responses in influencing the development of H. pylori infection in children and adults. 2. Assess the potential importance of the gastric microbiome in influencing the development and the degree of inflammation associated with H. pylori infection in children and adults. The results from these studies will be correlated with the immune responses in subjects in Aim 1 to determine the association of the gastric microbiome with specific immune responses to H. pylori infection in children and adults. 3. Assess the role of specific immunity and gastric microflora either in isolation or in concert with H. pylori infection, in influencing the development of gastroesophageal reflux disease, dyspepsia, gastric ulcers, duodenal ulcers and gastric cancer. These studies will generate new information about immunologic function and regulation in the stomach which would subsequently allow for comparison to gut immunity. Additionally, new information on the presence and possible contribution of other bacteria on gastric health and disease will provide significant advances for treatment of patients presenting with gastric pathology